• Title/Summary/Keyword: Activation Properties

Search Result 1,497, Processing Time 0.032 seconds

Inhibitory effects of the atypical antipsychotic, clozapine, on voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells

  • Kang, Minji;Heo, Ryeon;Park, Seojin;Mun, Seo-Yeong;Park, Minju;Han, Eun-Taek;Han, Jin-Hee;Chun, Wanjoo;Ha, Kwon-Soo;Park, Hongzoo;Jung, Won-Kyo;Choi, Il-Whan;Park, Won Sun
    • The Korean Journal of Physiology and Pharmacology
    • /
    • v.26 no.4
    • /
    • pp.277-285
    • /
    • 2022
  • To investigate the adverse effects of clozapine on cardiovascular ion channels, we examined the inhibitory effect of clozapine on voltage-dependent K+ (Kv) channels in rabbit coronary arterial smooth muscle cells. Clozapine-induced inhibition of Kv channels occurred in a concentration-dependent manner with an half-inhibitory concentration value of 7.84 ± 4.86 µM and a Hill coefficient of 0.47 ± 0.06. Clozapine did not shift the steady-state activation or inactivation curves, suggesting that it inhibited Kv channels regardless of gating properties. Application of train pulses (1 and 2 Hz) progressively augmented the clozapine-induced inhibition of Kv channels in the presence of the drug. Furthermore, the recovery time constant from inactivation was increased in the presence of clozapine, suggesting that clozapine-induced inhibition of Kv channels is use (state)-dependent. Pretreatment of a Kv1.5 subtype inhibitor decreased the Kv current amplitudes, but additional application of clozapine did not further inhibit the Kv current. Pretreatment with Kv2.1 or Kv7 subtype inhibitors partially blocked the inhibitory effect of clozapine. Based on these results, we conclude that clozapine inhibits arterial Kv channels in a concentration-and use (state)-dependent manner. Kv1.5 is the major subtype involved in clozapine-induced inhibition of Kv channels, and Kv2.1 and Kv7 subtypes are partially involved.

Gynostemma pentaphyllum extract and Gypenoside L enhance skeletal muscle differentiation and mitochondrial metabolism by activating the PGC-1α pathway in C2C12 myotubes

  • Kim, Yoon Hee;Jung, Jae In;Jeon, Young Eun;Kim, So Mi;Oh, Tae Kyu;Lee, Jaesun;Moon, Joo Myung;Kim, Tae Young;Kim, Eun Ji
    • Nutrition Research and Practice
    • /
    • v.16 no.1
    • /
    • pp.14-32
    • /
    • 2022
  • BACKGROUND/OBJECTIVES: Peroxisome proliferator-activated receptor-gamma co-activator-1α (PGC-1α) has a central role in regulating muscle differentiation and mitochondrial metabolism. PGC-1α stimulates muscle growth and muscle fiber remodeling, concomitantly regulating lactate and lipid metabolism and promoting oxidative metabolism. Gynostemma pentaphyllum (Thumb.) has been widely employed as a traditional herbal medicine and possesses antioxidant, anti-obesity, anti-inflammatory, hypolipemic, hypoglycemic, and anticancer properties. We investigated whether G. pentaphyllum extract (GPE) and its active compound, gypenoside L (GL), affect muscle differentiation and mitochondrial metabolism via activation of the PGC-1α pathway in murine C2C12 myoblast cells. MATERIALS/METHODS: C2C12 cells were treated with GPE and GL, and quantitative reverse transcription polymerase chain reaction and western blot were used to analyze the mRNA and protein expression levels. Myh1 was determined using immunocytochemistry. Mitochondrial reactive oxygen species generation was measured using the 2'7'-dichlorofluorescein diacetate assay. RESULTS: GPE and GL promoted the differentiation of myoblasts into myotubes and elevated mRNA and protein expression levels of Myh1 (type IIx). GPE and GL also significantly increased the mRNA expression levels of the PGC-1α gene (Ppargc1a), lactate metabolism-regulatory genes (Esrra and Mct1), adipocyte-browning gene fibronectin type III domain-containing 5 gene (Fndc5), glycogen synthase gene (Gys), and lipid metabolism gene carnitine palmitoyltransferase 1b gene (Cpt1b). Moreover, GPE and GL induced the phosphorylation of AMP-activated protein kinase, p38, sirtuin1, and deacetylated PGC-1α. We also observed that treatment with GPE and GL significantly stimulated the expression of genes associated with the anti-oxidative stress response, such as Ucp2, Ucp3, Nrf2, and Sod2. CONCLUSIONS: The results indicated that GPE and GL enhance exercise performance by promoting myotube differentiation and mitochondrial metabolism through the upregulation of PGC-1α in C2C12 skeletal muscle.

Whitening and inhibiting NF-κB-mediated inflammation properties of the biotransformed green ginseng berry of new cultivar K1, ginsenoside Rg2 enriched, on B16 and LPS-stimulated RAW 264.7 cells

  • Xu, Xing Yue;Yi, Eun Seob;Kang, Chang Ho;Liu, Ying;Lee, Yeong-Geun;Choi, Han Sol;Jang, Hyun Bin;Huo, Yue;Baek, Nam-In;Yang, Deok Chun;Kim, Yeon-Ju
    • Journal of Ginseng Research
    • /
    • v.45 no.6
    • /
    • pp.631-641
    • /
    • 2021
  • Background: Main bioactive constituents and pharmacological functions of ripened red ginseng berry (Panax ginseng Meyer) have been frequently reported. Yet, the research gap targeting the beneficial activities of transformed green ginseng berries has not reported elsewhere. Methods: Ginsenosides of new green berry cultivar K-1 (GK-1) were identified by HPLC-QTOF/MS. Ginsenosides bioconversion in GK-1 by bgp1 enzyme was confirmed with HPLC and TLC. Then, mechanisms of GK-1 and β-glucosidase (bgp1) biotransformed GK-1 (BGK-1) were determined by Quantitative Reverse Transcription-Polymerase Chain Reaction and Western blot. Results: GK-1 possesses highest ginsenosides especially ginsenoside-Re amongst seven ginseng cultivars including (Chunpoong, Huangsuk, Kumpoong, K-1, Honkaejong, Gopoong, and Yunpoong). Ginseng root's biomass is not affected with the harvest of GK-1 at 3 weeks after flowering period. Then, Re is bioconverted into a promising pharmaceutical effect of Rg2 via bgp1. According to the results of cell assays, BGK-1 shows decrease of tyrosinase and melanin content in α-melanocyte-stimulating hormone challenged-murine melanoma B16 cells. BGK-1 which is comparatively more effective than GK-1 extract shows significant suppression of the nuclear factor (NF)-κB activation and inflammatory target genes, in LPS-stimulated RAW 264.7 cells. Conclusion: These results reported effective whitening and anti-inflammatory of BGK-1 as compared to GK-1.

Core Promoter Mutation of ntC1731T and G1806A of Hepatitis B Virus Increases HBV Gene Expression (B형 간염 바이러스의 ntC1731T 및 G1806A의 core 프로모터 돌연변이에 의한 HBV 유전자 발현 증가 분석)

  • Cho, Ja Young;Yi, Yi Kyaw;Seong, Mi So;Cheong, JaeHun
    • Journal of Life Science
    • /
    • v.32 no.2
    • /
    • pp.94-100
    • /
    • 2022
  • Chronic infection by hepatitis B virus (HBV) greatly increases the risk for liver cirrhosis and hepatocellular carcinoma (HCC). The outcome of HBV infection is shaped by the complex interplay of the mode of transmission, host genetic factors, viral genotype, adaptive mutations, and environmental factors. The pregenomic RNA transcription of HBV for their replication is regulated by the core promoter activation. Core promoter mutations have been the reason for acute liver failure and are associated with HCC development. We obtained HBV genes from a patient in Myanmar who was infected with HBV and identified gene variations in the core promoter region. For measuring the relative transactivation activity of the core promoter, we prepared the core-promoter reporter construct. Among the gene variations of the core promoter, the mutations of C1731T and G1806A were associated with increase in the transactivation of the HBV core promoter. Through computer analysis for searching for a tentative transcription factor binding site, we showed that the mutations of C1713T and G1806A newly created C/EBPβ and XBP1-responsive elements of the core promoter, respectively. The ectopic expression of C/EBPβ largely increased the HBV core promoter containing the C1713T mutation and that of XBP1 activated the M95 promoter containing the G1806A mutation. Our efforts to treat and prevent HBV infections are hampered by the emergence of drug-resistant mutations and vaccine-escape mutations. Our results provide the biological properties and clinical significance of specific HBV core promoter mutations.

Inhibitory Effect of Extract of Trogopterorum Faeces on the Production of Inflammatory Mediaters (오령지 추출물의 염증성 세포활성물질 억제효과)

  • Kim, Byung-Jin;Ham, Kyung-Wan;Park, Kyung-Bae;Kim, Dae-Hyeon;Jo, Beom-Yeon;Cho, Chang-Re;Cho, Gil-Hwan;Bae, Gi-Sang;Park, Kyoung-Chel;Koo, Bon-Soon;Kim, Min-Sun;Song, Ho-Joon;Park, Sung-Joo
    • The Korea Journal of Herbology
    • /
    • v.24 no.3
    • /
    • pp.153-160
    • /
    • 2009
  • Objectives : The purpose of this study was to investigate the anti-inflammatory effects of extract from Trogopterorum Faeces (TF) on the RAW 264.7 cells. Methods : To prove the TF's anti-inflammatory effects, we investigated nitric oxide (NO) production and own cell viability. We examined the cytokine productions on lipopolysacchride (LPS)-induced RAW 264.7 cells and also cellular regulatory mechanisms. Results : TF does not have any cytotoxic effect. TF reduced LPS-induced NO production, interleukin (IL)-1b, IL-6, IL-10 and tumor necrosis factor-a (TNF-a) in RAW 264.7 cells. TF inhibited the activation of mitogen-activated protein kinases (MAPKs) such as p38, extracelluar signal-regulated kinase (ERK 1/2) and c-Jun NH2-terminal kinase (JNK) and also the degradation of inhibitory kappa B a (Ik-Ba) in the LPS-stimulated RAW 264.7 cells. TF reduced the serum levels of IL-1b, IL-6, TNF-a. The survival rate of LPS-induced endotoxin shock was increased by TF administration. Conclusions : TF down-regulated LPS-induced NO and cytokines production, which could provide a clinical basis for anti-inflammatory properties.

Toxicity assessment of food additive(E171) in aquatic environments (식품첨가물 E171이 수생물에 미치는 독성 평가)

  • In-Gyu Song;Kanghee Kim;Hakwon Yoon;June-Woo Park
    • Korean Journal of Environmental Biology
    • /
    • v.41 no.1
    • /
    • pp.41-53
    • /
    • 2023
  • E171, a mixture of titanium dioxide, has been widely used as a food additive due to its whitening effect and low toxicity. However, it has been proven that E171 is no longer safe for public health. So far, there are insufficient studies on the toxic effects of E171 on organisms especially using standardized test methods. In this study, toxicity assessments of E171 to two aquatic species, water flea (Daphnia magna) and zebrafish (Danio rerio), were performed using modified standardized test methods based on the physicochemical properties of E171. The hydrodynamic diameter, polydispersity index, and turbiscan stability index (TSI) were measured to ensure the dispersion stability of E171 in exposure media during the test period. The EC50 for immobilization of water flea was 141.7 mg L-1 while zebrafish was not affected until 100 mg L-1 of E171. Measurements of reactive oxygen species (ROS) and antioxidant enzyme activities confirmed that E171 induced oxidative stress, leading to the activation of superoxide dismutase and catalase in both water flea and zebrafish, although the expression of antioxidant enzyme genes differed between species. These results suggested the potential risk of E171 to aquatic organisms and provided toxicological insights into the impacts of E171 on the environment.

Desmarestia tabacoides Ameliorates Lipopolysaccharide-induced Inflammatory Responses via Attenuated TLR4/MAPKs/NF-κB Signaling Cascade in RAW264.7 Cells (RAW 264.7 세포에서 담배잎산말의 TLR4/MAPKs/NF-κB 신호전달체계 조절을 통한 항염증 효과)

  • Hyun-Seo Yoon;Hyun An;Chung Mu Park
    • Journal of Life Science
    • /
    • v.33 no.6
    • /
    • pp.463-470
    • /
    • 2023
  • Desmarestia tabacoides Okamura is a brown macroalgae that is found worldwide. Although several genera of Desmarestia have been reported as having anti-tumorigenic, anti-melanogenic, and photoprotective properties, the anti-inflammatory activity of D. tabacoides Okamura has not yet been evaluated. In this study, we analyzed the anti-inflammatory mechanisms of D. tabacoides Okamura ethanol extract (DTEE) via the inhibition of nitric oxide (NO) and prostaglandin (PG) E2 production and the expression of their corresponding enzymes, inducible NO synthase (iNOS), and cyclooxygenase (COX)-2. In addition, their upstream signaling molecules were evaluated by Western blot analysis, such as nuclear factor (NF)-κB, mitogen-activated protein kinase (MAPK), and phosphoinositide-3-kinase (PI3K)/Akt, in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. The DTEE treatment significantly inhibited LPS-induced NO and PGE2 production as well as the expression of their corresponding enzymes, iNOS, and COX-2 without cytotoxicity. The stimulated transcription factor NF-κB and upstream signaling molecules extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38 were attenuated by the DTEE treatment, which was statistically significant, while Akt did not provide any inhibitory effect. Moreover, the DTEE treatment significantly mitigated the LPS-activated adaptor molecules, toll-like receptor 4 (TLR4), and myeloid differentiation primary response 88 (MyD88) in the RAW 264.7 cells. These results suggest that DTEE attenuates TLR4-mediated inflammatory responses by inhibiting NF-κB activation and suppressing MAPK phosphorylation in LPS-stimulated RAW 264.7 cells.

Effect of Impregnation and Modification on Activated Carbon for Acetaldehyde Adsorption (아세트알데하이드 흡착을 위한 활성탄의 첨착 및 개질 효과)

  • Jin Chan Park;Dong Min Kim;Jong Dae Lee
    • Korean Chemical Engineering Research
    • /
    • v.61 no.3
    • /
    • pp.472-478
    • /
    • 2023
  • In this study, the acetaldehyde removal characteristics of activated carbon (AC) for air purifier filters were investigated using metal catalysts-impregnation and functional group-modification method. The AC with a high specific surface area(1700 m2/g) and micropores was prepared by KOH activation of coconut charcoal and the efficiency of catalyst and functional group immobilization was examined by varying the drying conditions within the pores after immersion. The physical properties of the prepared activated carbon were analyzed by BET, ICP, EA, and FT-IR, and the acetaldehyde adsorption performances were investigated using gas chromatography (GC) at various impregnation and modified conditions. As the concentration of impregnation solution increased, the amount of impregnated metal catalysts increased, while the specific surface area showed a decreasing trend. The adsorption tests of the metal catalyst-impregnated and functional group-modified activated carbons revealed that excellent adsorption performance in compositions MgO10@AC, CaO10@AC, EU10@AC, and H-U3N1@AC, respectively. The MgO10@AC, which showed the highest adsorption performance, had a breakthrough time of 533.8 minutes and adsorption capacity of 57.4 mg/g for acetaldehyde adsorption. It was found that the nano-sized MgO catalyst on the activated carbon improved the adsorption performance by interacting with carbonyl groups of acetaldehyde.

Effect of sweet pumpkin powder on lipid metabolism in leptin-deficient mice (Leptin 유전자 결핍 동물모델에서 단호박분말 투여가 지방대사변화에 미치는 영향)

  • Inae Jeong;Taesang Son;Sang-myeong Jun;Hyun-Jung Chung;Ok-Kyung Kim
    • Journal of Nutrition and Health
    • /
    • v.56 no.5
    • /
    • pp.469-482
    • /
    • 2023
  • Purpose: Obesity has emerged as a critical global public health concern as it is associated with and increases susceptibility to various diseases. This condition is characterized by the excessive enlargement of adipose tissue, primarily stemming from an inequity between energy intake and expenditure. The purpose of this study was to investigate the potential of sweet pumpkin powder in mitigating obesity and metabolic disorders in leptin-deficient obese (ob/ob) mice and to compare the effects of raw sweet pumpkin powder (HNSP01) and heat-treated sweet pumpkin powder (HNSP02). Methods: Leptin-deficient obese mice were fed a diet containing 10% HNSP01 and another containing 10% HNSP02 for 6 weeks. Results: The supplementation of ob/ob mice with HNSP01 and HNSP02 resulted in decreased body weight gain, reduced adipose tissue weight, and a smaller size of lipid droplets in the adipose tissue and liver. Furthermore, the ob/ob-HNSP01 and ob/ob-HNSP02 supplemented groups exhibited lower levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol, fasting blood glucose, and insulin, as well as a reduced atherogenic index in comparison with the control group. Molecular analysis also demonstrated that the intake of HNSP01 and HNSP02 resulted in a diminished activation of factors associated with fatty acid synthesis, including acetyl-CoA carboxylase and fatty acid synthase, while concurrently enhancing factors associated with lipolysis, including adipose triglyceride lipase and hormone-sensitive lipase, in the adipose tissue. Conclusion: Taken together, these findings collectively demonstrate the potential of sweet pumpkin powder as a functional food ingredient with therapeutic properties against obesity and its associated metabolic disorders, such as insulin resistance and dyslipidemia.

Conductive Performance of Mortar Containing Fe-Activated Biochar (Fe에 의해 활성화된 목질계 바이오차를 혼입한 모르타르의 전도성능)

  • Jin-Seok Woo;Ai-Hua Jin;Won-Chang Choi;Soo-Yeon Seo;Hyun-Do Yun
    • Journal of the Korea institute for structural maintenance and inspection
    • /
    • v.28 no.2
    • /
    • pp.27-34
    • /
    • 2024
  • This study was conducted to examine the feasibility of using Fe-activated wood-derived biochar as a conductive filler for manufacturing cement-based strain sensor. To evaluate the compressive and electrical properties of cement composite with 3% Fe-activated biochar, three cubic specimens of size 50 x 50 x 50mm3 and three prismatic cement-based sensors of size 40 x 40 x 80mm3 were prepared respectively. The four-probe method of electrical resistance measurement was used for cement-based sensors. For cement-based sensors with FE-activated biochar, the conductive performance such as electrical resistance and impedance under different water content and repeated compression was investigated. Results showed that the fractional changes in the DC electrical resistivity of cement-based sensors increase with increasing time and the maximum fractional changes in the resistivity decrease with increasing the moisture contents during 900s. At moisture content of 7.5% range, the conductive performance of cement composite including 3% Fe-activated biochar as a conductive filler showed the most stable, while the strain detection ability tended to decrease somewhat as the repeated compressive stress increased between repeated compressive strain and fractional change in resistivity (FCR).